Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells

// Agota Tűzesi 1 , Teresia Kling 1 , Anna Wenger 1 , Taral R. Lunavat 2 , Su Chul Jang 2 , Bertil Rydenhag 3 , Jan Lotvall 2 , Steven M. Pollard 4 , Anna Danielsson 5 and Helena Caren 1 1 Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 2 Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden 3 Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 4 MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh BioQuarter, Edinburgh, UK 5 Sahlgrenska Cancer Center, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Correspondence to: Helena Caren, email: helena.caren@gu.se Keywords: microRNA, exosomes, cancer stem cells, glioma, pediatric Received: July 28, 2016      Accepted: August 19, 2017      Published: October 06, 2017 ABSTRACT High-grade gliomas (HGGs) are very aggressive brain tumors with a cancer stem cell component. Cells, including cancer stem cells, release vesicles called exosomes which contain small non-coding RNAs such as microRNAs (miRNAs). These are thought to play an important role in cell-cell communication. However, we have limited knowledge of the types of exosomal miRNAs released by pediatric HGG stem cells; a prerequisite for exploring their potential roles in HGG biology. Here we isolated exosomes released by pediatric glioma stem cells (GSCs) and compared their repertoire of miRNAs to genetically normal neural stem cells (NSCs) exosomes, as well as their respective cellular miRNA content. Whereas cellular miRNAs are similar, we find that the exosomal miRNA profiles differ between normal and tumor cells, and identify several differentially expressed miRNAs. Of particular interest is miR-1290 and miR-1246, which have previously been linked to ‘stemness’ and invasion in other cancers. We demonstrate that GSC-secreted exosomes influence the gene expression of receiving NSCs, particularly targeting genes with a role in cell fate and tumorigenesis. Thus, our study shows that GSCs and NSCs have similar cellular miRNA profiles, yet differ significantly in the repertoire of exosomal miRNAs and these could influence malignant features of HGG.